The Interleukin-2-Deficient Mouse Model

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Abstract
Interleukin-2-deficient (IL-2–/–) mice develop colitis with striking clinical and morphological similarities to ulcerative colitis. Since transport and barrier properties are impaired in ulcerative colitis, we studied transport and barrier functions in IL-2–/– mice in order to gain insight for the first time into the general pathomechanisms of disturbed transport and barrier function of the intestine during inflammation. Alternating current impedance analysis was used to determine tissue conductance in the inflamed proximal colon of IL-2–/– mice and to discriminate between pure epithelial and subepithelial conductance. Surprisingly, epithelial conductance was not increased but diminished in IL-2–/– mice compared to controls (20.2 ± 1.3 versus 28.8 ± 2.8 mS/cm2). Concomitantly, conductance of the subepithelial tissue layers was decreased in IL-2–/– mice as a result of edema and infiltration with inflammatory cells. In the distal colon, electrogenic Na+ transport (JNa) mediated by the epithelial Na+ channel (ENaC) was measured 8 h after stimulation with 3·10–9M aldosterone in vitro as the drop in ISC (short circuit current) after addition of 10–4M amiloride. In controls, JNa was 6.9 ± 0.9 µmol·h–1·cm–2, whereas it was abolished in IL-2–/– mice. In conclusion, the inflamed colon of IL-2–/– mice exhibits a severe disturbance in Na+ uptake via the ENaC in the absence of a barrier defect. Thus, reduced expression of active absorptive transport and not a barrier defect is responsible for the diarrhea in this model of intestinal inflammation. This makes this model suitable for studying the general pathomechanisms of the inflammatory downregulation of intestinal transport proteins.